CAR T Cell Therapy for Human Immunodeficiency Virus
CAR T Cell Therapy for Human Immunodeficiency Virus
Mahsa Khatibi,1Amir Gholamzad,2Ghazaleh Daryoushi,3Mahdi Nakhaee,4Mehrdad Gholamzad,5,*
1. Department of Laboratory Medicine, Faculty of Paramedical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 2. Department of Laboratory Medicine, Faculty of Paramedical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 3. Department of Laboratory Medicine, Faculty of Paramedical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 4. Department of Laboratory Medicine, Faculty of Paramedical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 5. Department of Microbiology and Immunology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Introduction: Cell-based immunotherapies have made enormous progress over the last decade with the approval of several anti-CD19-chimeric antigen receptors (CAR)-T cell therapies for hemato-oncological diseases. CARs are synthetic receptors comprising an antigen-specific extracellular domain fused to a hinge, transmembrane and intracellular signaling domains. The success obtained with CD19 CAR-T cells rekindled interest in using CAR-T cells to treat HIV seropositive patients.
Methods: The purpose of this review is to discuss historical and recent developments of HIV Patient CAR T Cell Therapies.
Results: Since the first description of CD4+-based CARs in the early 90s, new generations of anti-HIV CARs were developed. They target the hetero-trimeric glycoprotein gp120/gp41 and consist of either a CD4+ extracellular domain or a VH/VL segment derived from broadly neutralizing antibodies. Recent efforts were employed in multiplexing CAR specificities, intracellular signaling domains and T cells resistance to HIV.
Conclusion: Several new-anti HIV CAR-T cells were successfully tested in preclinical mice models and are now waiting to be evaluated in clinical trials. One of the key parameters to successfully using CAR-T cells in HIV treatment will depend on their capacity to control the HIV reservoir without causing off-targeting activities.
Keywords: CAR T Cell Therapy, Chimeric antigen receptor T-cell therapy, HIV, AIDS